Process for the preparation of peptides

Abstract

The present invention relates to a process for the preparation of peptides using an excess of an activated carboxylic component to acylate an amino component, wherein after the acylation an amine comprising a free anion or a latent anion is used as a scavenger of residual activated carboxylic functions. This process is useful for the preparation of oligo- and polypeptides and, more generally, in the preparation of compounds containing one or more amide bonds.

1. A process for the preparation of a compound containing one or more amide bonds using an excess of activated carboxylic component to acylate an amino component, wherein after completion of the acylation reaction an amine comprising a latent anion is added as a scavenger of the residual activated carboxylic functions, which latent anion bears a temporary protecting group which can be selectively removed, followed by a deprotection step resulting in hydrophilic scavenged compounds which may be actively extracted into a basic aqueous phase. 
     
     
       2. The process of  claim 1  wherein the temporary protecting group is selectively removed in the presence of a permanent protecting group. 
     
     
       3. The process of  claim 1  wherein the compound being prepared is a peptide. 
     
     
       4. The process of  claim 2  where the permanent protecting group is attached to the compound. 
     
     
       5. The process of  claim 1  wherein the latent anion in the scavenging amine bears a temporary protecting group which displays a lability similar to that of the temporary protecting group present at the N-terminus of the growing compound. 
     
     
       6. The process of  claim 1  herein the temporary protecting group is a hydrogenolytically removable groups. 
     
     
       7. The process of  claim 2  wherein the permanent protecting group is an acidolytically removable group. 
     
     
       8. The process of  claim 6  wherein the temporary protecting group is of the benzyl type. 
     
     
       9. The process of  claim 1  wherein the scavenger is a primary amine. 
     
     
       10. The process of  claim 9  wherein the primary amine is a C-terminally protected amino acid derivative. 
     
     
       11. The process of  claim 10  wherein the amino acid is β-alanine or a derivative thereof. 
     
     
       12. The process of  claim 1  wherein the scavenger is a benzyl β-alaninate or a salt thereof. 
     
     
       13. The process of  claim 1  comprising performing the process in solution. 
     
     
       14. The process of  claim 1  further comprising an aqueous extraction step.